Positioning device for a sample carrier

ABSTRACT

The invention relates to an apparatus for positioning a sample carrier plate, wherein the apparatus comprises a main body for receiving the sample carrier plate, positioning stops which are disposed in opposing first corner regions of the main body and are prestressed for clamping the sample carrier plate and mounted displaceably, an actuating device which is disposed at the main body and is equipped such that by actuating the actuating device the positioning stops can be transferred between an operating state engaging the sample carrier plate and an operating state releasing the sample carrier plate, and comprises a force transmitting element which is equipped to transmit an actuating force from the actuating device to the positioning stops.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/257,120, which is a U.S. National Phase of International ApplicationNo. PCT/EP2010/053556, filed Mar. 18, 2010, designating the U.S. andpublished on Sep. 23, 2010 as WO 2010/106147, which claims priority toGerman Patent Application No. 10 2009 013 778.5, filed Mar. 18, 2009.The content of each of these applications is incorporated herein byreference in its entirety.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication, and any and all priority claims identified therein, arehereby incorporated by reference under 37 CFR 1.57.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to an apparatus for positioning a sample carrierplate.

The invention further relates to a method for positioning a samplecarrier plate.

2. Description of the Related Art

The microtiter plate has been established as standard for thesimultaneous processing of a large number of small sample volumes inmolecular biology. This comprises a rectangular plate of fixeddimensions, which contains a defined number of isolated cavities (wells)in rows and columns. Inside these wells different samples can be testedfor their properties independently of one another. Microtiter plateshaving 96, 384, or 1536 wells are usually widely used in pharmaceutical,chemical, and biological research.

With increasing degree of automation and the increase in the number ofwells in a microtiter plate, there is a tendency to automate fillingprocesses and other processes. Various types of pipetting heads areknown for simultaneously filling the wells, which heads can accommodatea number of pipetting tips corresponding to the number of wells.

The greater the number of wells of the corresponding microtiter plate,the smaller the diameter of each of these indentations. The requirementson the positioning accuracy of microtiter plate to pipetting headtherefore increase. Furthermore, in a large number of application inpharmaceutical, chemical, and biological research it is necessary toensure thorough mixing of the components in the wells of the microtiterplate. A simple possibility for influencing the local concentration andtherefore the probability of interaction of the reaction partners is anexternal energy input by defined movement (shaking) of the reactioncontainer. The advantage of such a method is the freedom fromcontamination as a result of the noncontact energy input (in contrast tomethods using moving mixing tools). Furthermore, due to this mixingmovement of a shaking apparatus, the homogenization of the temperaturewithin the sample is also accelerated with respect to the compensatingprocesses naturally present.

Manufacturing tolerances in the production of microtiter plates inlength, width, and base height act directly on the positioning of themicrotiter plate since the microtiter plate is conventionally frequentlydisplaced by springs toward solid obstacles.

In case of conventional systems positioning pieces are often firmlyattached for fixing microfilter plates during the process of pipettingand shaking. It is the object of the positioning pieces to always holdthe microtiter plate in position. Springs can be contained in thesepositioning pieces. However, the spring force produced should be sogreat that the microtiter plate is held in position against thecentrifugal force produced by the orbital mixing movement. Due to thehigh force required, the insertion of the microtiter plates into theshaking apparatus by the transporting apparatus (for example, gripperarm) of a robot can possibly be difficult or impossible. It is thereforeproblematical to fundamentally dispense with resilient elements since aclearance is then required in the receiving area as a result of thementioned manufacturing tolerances (for example, ±0.5 mm), which in anunfavorable case can be 1 mm. Such a clearance allows undesirablemovements of the microtiter plate during the shaking process and alsoconflicts with the aim of a precise positioning of the microtiter plate,in particular in the case of microtiter plates having 1536 wells, whosediameter for example is around 1 mm.

EP 1,186,891 discloses that in order to enable the spatial alignment ofa support plate, this has a joint head on the underside which lies in ajoint socket of a support plate. A connector of the joint head is guidedthrough a central opening of the joint socket, which bears a clampingring abutting against the outer side of the joint socket, which can bepressed by means of a tensile slip for fixing the alignment of thesupport plate. Two diagonally outwardly displaceable centering stopslocated opposite one another in a mirror-inverted manner on the upperside of the support plate are fastened to diagonally displaceablesliders. These engage at the opposite ends of a rotatable coupling leverwith the same. This lever sits on a vertical shaft, which extends fromthe underside of the support plate through a hole in the joint head asfar as the end of the connector. There said lever carries an actuatinglever which can be rotated against the restoring force of a spiralspring for movement of the centering stops outward to allow a loweringor lifting of a microtiter plate.

WO 86/07232 discloses an apparatus for positioning a circuit panel.

EP 1,111,391 discloses a device for holding an item, in particular amicrotiter plate, comprising a laying surface, where a stop limiting thedisplacement of the item on one side in the plane of the same isprovided in the area of the laying surface, as well as a clampingapparatus having a clamping part that can be retracted with respect tothe stop against a pretension.

DE 10 2004 021 664 discloses a microtiter plate shaking apparatuscomprising a vibratory plate which has a reception zone for themicrotiter plate and positioning pieces disposed thereon for themicrotiter plate to be held. At least one positioning piece is movablymounted and can be moved between a working position and a releaseposition. The at least one movably mounted positioning piece is movablefrom the working into the release position by means of a drive.

WO 99/13339 discloses a positioning apparatus for positioning amicrotiter plate. A positioning platform can be provided in asurrounding platform. A further platform can be provided in thepositioning platform. The surrounding platform has actuators. A movablecarrier platform of the positioning platform can be moved relative tothe carrier platform. In this case, bulk-like elements are disposedalong the longitudinal side between the innermost further platform andthe surrounded positioning platform. By means of a fluid such ascompressed air, for example, the bulk-like elements can absorb fluid orblow out fluid so that a movement and positioning of the innersurrounded platform can thereby be implemented.

It is still difficult to position a sample receiving container preciselyon a substrate.

SUMMARY OF THE INVENTION

It is the object of the invention to position a sample receivingcontainer precisely on a substrate.

This object is solved by an apparatus for positioning a sample carrierplate and a method for positioning a sample carrier plate having thefeatures according to the independent patent claims.

According to an exemplary embodiment of the present invention, anapparatus for positioning a sample carrier plate (for example, arectangular sample carrier plate) is provided, wherein the apparatuscomprises a main body (for example, a base body having a rectangularshape, on and/or in which at least a part of the remaining components ofthe apparatus is disposed) for receiving the sample carrier plate (forexample, a base surface of the sample carrier plate), positioning stops,which are disposed in (in particular diagonally) opposing first cornerregions of the main body and are prestressed (for example, with a springforce acting in a clamping manner to a midpoint of the main body) forclamping the sample carrier plate (for example, from opposite cornerregions of the sample carrier plate) and mounted displaceably (forexample, linearly displaceably by means of a guide rail or displaceablediagonally outward or inward with one another in some other way in amirror-inverted manner), an actuating device (for example, an actuatordevice by which means an operating state of the apparatus can be set)which is disposed in a second corner region of the main body and isequipped such that by actuating the actuating device, the positioningstops can be transferred between an operating state engaging the samplecarrier plate and an operating state releasing the sample carrier plate(where the positioning stops are localized in the releasing operatingstate further from the center with respect to the midpoint of the mainbody than in the engaging operating state) and a (for example, rotatablymounted) force transmitting element (for example a circular disk) whichis equipped to transmit (in particular deflect or other conversion offorce) an actuating force from the actuating device to the positioningstops.

The arrangement of the actuating device in a second corner region of themain body is optional. In other exemplary embodiments the actuatingdevice can be disposed in another area of the main body, for example,along a side edge or at a certain distance from the corner region. Everyfeature disclosed in this description is also applicable to an exemplaryembodiment in which the actuating device is not disposed in a cornerregion of the main body.

According to another exemplary embodiment of the present invention, amethod is provided for positioning a sample carrier plate, where themethod comprises receiving the sample carrier plate on a main body,clamping the sample carrier plate on prestressed and displaceablymounted positioning stops, which are disposed in opposite first cornerregions of the main body, actuating an actuating device disposed in asecond corner region of the main body for transferring the positioningstops between an operating state engaging the sample carrier plate andan operating state releasing the sample carrier plate, and transmittingan actuating force from the actuating device to the positioning stops bymeans of a force transmitting element.

A corner region of the main body can be understood in particular as aspatial position at which outer or inner edges of the main body or acarrier abut against one another at an angle, in particularsubstantially orthogonally (although a certain rounding in such cornerregions does not need to be excluded). The corresponding component canthen be disposed or be disposable spatially at or directly adjacent tosuch a position.

According to an exemplary embodiment, a positioning system is providedfor the precise positioning of a sample carrier plate such as, forexample, a microtiter plate, where the sample carrier plate can besupported from a lower side by a main body of the apparatus, can besupported in corner regions by mutually opposite positioning stops ofthe apparatus and the positioning stops can be moved manually orautomatically by an actuating device positioned in a corner region ofthe main body such that this can either enable a forceless placement ofthe sample carrier plate on the main body without clamping action of thepositioning stops or a nonpositive or positive centering of the samplecarrier plate. In the latter operating state the positioning stopsclearly press onto opposite corners of the, for example, rectangularsample carrier plate from two opposite directions so that this can bepositioned two-dimensionally symmetrically in a predefinable mannerunder the influence of the clamping action. The high positioningaccuracy that can be achieved with an apparatus according to anexemplary embodiment of the invention is in particular based on the factthat a central force transmission element can be disposed in a centralsection of the apparatus, in particular in the vicinity of a center ofthe apparatus, which is in operative communication with the positioningstops disposed in the opposite corner regions and the actuating devicedisposed in another corner region. The user can thereby undertake anactuator movement at the actuating device in a simple manner in a cornerregion, for example, a simple sliding movement, which sets in motion adeterministic force transmission mechanism through which the twopositioning stops ultimately exert corresponding clamping forces onopposite corners of the sample carrier plate. This not only guarantees ahighly accurate positioning of the sample carrier plate with respect tothe apparatus but also leads to a reliable actuatability. In addition,the system is mechanically stable even when this system is to beoperated with the highest precision requirement (for example, when thesample carrier plate has a plurality of liquid wells in which fluids areto be injected by means of a pipetting robot and/or when a definedshaking movement, for example, an orbital movement, is applied to thesample carrier plate for mixing the fluidic samples).

Additional exemplary embodiments of the apparatus are describedhereinafter. These are also valid for the method. The apparatus can beequipped for centering the sample carrier plate with respect to amidpoint (or another predefined reference point) of the main body. Forexample, for automatic pipetting requirements it can be desirable toposition the sample carrier plate in a spatially very precisely definedmanner with respect to the apparatus so that a corresponding positionsignal can be transmitted to the pipetting apparatus, which enablespositionally accurate pipetting or the like. According to the exemplaryembodiment described, the prestress and the arrangement of thepositioning stops can be configured such that in the absence of a forceapplied by a user, the sample carrier plate is again and again pushedback into the center of the apparatus. This is accomplished withoutcomplex alignment but can be accomplished merely by force couplingbetween the two positioning stops and the force transmission element aswell as the actuating device while simultaneously exerting apredetermined prestress, which can act on the positioning stops.

The apparatus can in particular be equipped for positioning a microtiterplate as a sample carrier plate. A microtiter plate can be understood inparticular as a laboratory device for investigating sample properties,for example, for an absorption measurement in photometers or for highthroughput screening tests in pharmaceutical and plant protectionresearch. Such a microtiter plate can comprise a rectangular plasticplate, which however can also be made of glass and other materials. Sucha microtiter plate can contain many saucers or wells, which are isolatedfrom one another, in rows and columns. Dimensions of some microtiterplates are standardized. Consequently, a standardized microtiter platecan be centered highly accurately or positioned otherwise in apredefinable manner using the positioning apparatus according to theinvention, which substantially simplifies cooperation with othercomponents (automatic pipetting apparatus or photometer arrangement).

The main body can comprise an adapter plate which can be equipped forreceiving the sample carrier plate. This adapter plate can be speciallyadapted to a quite specific sample carrier plate. For example, a formcoding of the adapter plate can correspond with a corresponding formcoding of the sample carrier plate so that an incorrect placement of thesample carrier plate on the adapter plate is avoided since a formclosure can be avoided in such a case.

For example, the adapter plate can be a flat adapter plate having aplane surface facing the sample carrier plate for positive receipt of aflat sample carrier plate. If the sample carrier plate has a flat base,the upper-side flat surface of the adapter plate can be provided tocorrespond to this sample carrier plate.

The main body can have a recess (for example, a cavity) on its surfacefacing the sample carrier plate, in which the flat adapter plate can beinserted so that it ends flush on an upper side and in a preciselyfitting manner. Such a recess can, for example, be a substantiallyrectangular hole on an upper side of the main body which can be shapedand dimensioned in order to be able to precisely receive an adapterplate. After receiving the adapter plate in such a recess, the commonupper-side surface of main body and adapter plate can be planar.Consequently, any tilting or incorrect positioning of the sample carrierplate on the adapter plate can be reliably avoided.

Alternatively to a flat surface, the adapter plate can have a surfacestructure or a topography which can be equipped for the positive receiptof a sample carrier plate having a surface structure or topographycomplementary to the surface structure or topography of the adaptersurface. Consequently, an inverse form can be provided on the upper sideof the adapter plate and on the lower side of the sample carrier plate,whereby the stability of the connection between adapter plate and samplecarrier plate can be further improved. For example, such a surfacestructure of the adapter plate can be an arrangement of saucers having acircular cross-section, which are formed to correspond with circularprojections on a lower side of the adapter plate.

The adapter plate can comprise a temperature-control unit integratedtherein for controlling the temperature of a fluidic sample which can bereceived in the sample carrier plate. Such a temperature-control unitcan, for example, be an Ohmic temperature control unit which enables aheating of the adapter plate and therefore the fluids of the samplecarrier plate by means of Ohmic losses of an electric current flowingthrough the adapter plate. Alternatively, such a temperature control canoptionally comprise a heating or a cooling, which can be achieved, forexample, by means of a Peltier element. Other temperature-controlsystems, for example using a cooling or heating medium (for example,water) flowing through a cavity in the adapter plate can also be used.By means of such a temperature control, for example, either thetemperature of a sample can be kept constant or alternatively apredetermined temperature cycle can be run through. The latter can beadvantageous or desirable, for example, for PCR analyses (“polymerasechain reaction”). The temperature-control unit can be adjustable in auser-defined manner or can function independently or in a regulatedmanner. For example, the temperature control unit can be regulated to acertain temperature based on a temperature measured by a temperaturesensor.

As a result of the various functions of the adapter plate (for example,holding, temperature control, other functions are possible), it ispossible to exchange the adapter plate specially adapted to the needs ofan analysis or mount it on the main body to increase the flexibility.For example, a set of several different adapter plates can be used forthis purpose, which can also be mounted in the recess of the main body.

The positioning stops can be disposed exclusively in two opposite firstcorner regions of the main body. In other words, according to anexemplary embodiment of the invention, a first corner region of arectangular main body can be provided with a first positioning stop anda diagonally opposite second corner region of the rectangular main bodycan be provided with a second positioning stop. The other two cornerregions of the apparatus can then be free from corresponding positioningstops. By using precisely two corresponding and opposite pairs ofpositioning pieces, both a clamping of corners of the sample carrierplate and therefore a secure positioning can be achieved and also anoverdetermination of positioning points can be avoided, which can thenlead to an imprecise positioning of the sample carrier plate in theapparatus. Such a configuration is at the same time easy to handle andresults in a low weight and small design of the apparatus.

In addition, by providing positioning stops at precisely two oppositecorner regions of the main body, a type of X structure (compare FIG. 1)of the force coupling is achieved, which can be achieved by the twopositioning stops and corresponding coupling rod as well as theactuating device with a corresponding coupling rod and a prestressingdevice with a corresponding coupling rod. This results in an efficientand very stable arrangement which can be switched between a rigidoperating mode and a flexible operating mode by means of a singlehandle.

The positioning stops in each first corner region can be formed by meansof two stop elements having two mutually perpendicular stop lines forplacement on a rectangular sample carrier plate. In other word, in eachcorner region in which a longitudinal edge and an orthogonal transverseedge of the sample carrier plate are to be fastened, a first stopelement is provided which applies a force component in a first directionto the sample carrier plate. A second stop element that generates asecond force component perpendicular to the first direction can furtherbe provided. An inner line (or an inner surface) of the respective stopelement thereby rests along a, for example, straight line against theside wall surface of the sample carrier plate.

Alternatively, the positioning stops in each first corner region can beformed by means of two stop elements having a round cross-section forplacement on the sample carrier plate. Such a stop element having around cross-section can, for example, be a cylindrical pin, inparticular a circular cylindrical pin, or a conical pin. A circularcylindrical pin has the advantage of a low expenditure and can clearlyact with a point coupling on a corresponding point of the sample carrierplate. Conical pins have the advantage of a high flexibility and can,for example, taper toward the main body on which they can be mounted. Anormal force between main body and sample carrier plate can be producedby the tapering of the conical pins toward the main body.

It is also possible to form the positioning stops as pins having acircular cylindrical section and a conical section. In particular, asection mounted on the main body can be circular cylindrical and anupper section adjoining the circular cylindrical section can be conical.This can lead to a gain in space when handling or lifting out componentssuch as a plate, for example.

The positioning pins for clamping can be equipped, to fix microplateshaving different web heights. In particular, the positioning pins can beformed to support web heights of 2.5 mm, 4.0 mm, and 6.1 mm. For thispurpose, the pins can be designed as pins having in particular threeO-rings becoming larger toward the top, where the O rings act on theupper microtiter plate web edge. It is also possible to design the pinsof solid material (for example, stainless steel) having correspondingphases and edges. The beveled edges substantially correspond to thefunction of the O-rings.

Consequently, the stop elements can be formed as pins having a pluralityof rings of different outside diameter mounted thereon. Such rings can,for example, be made of a flexible material such as, for example,rubber. It is possible that an outside diameter of a respective ring isgreater, the further away such a ring is located from the carrierelement. This enables microtiter plates of different sizes to beinserted into the device.

Alternatively the stop element can be formed as pins having a pluralityof steps of different outside diameter formed integrally thereon. Suchsteps can, for example, be fabricated as one-piece or one-material witha core of the pins. It is possible that an outside diameter of arespective step is greater, the further away such a step is located fromthe carrier element. This enables microtiter plates of different sizesto be inserted into the device.

Each of the positioning stops can be assigned a first linear guideelement in or on which the respective positioning stop can be mountedlinearly displaceably. Such a linear guide element can comprise anelongate hole along which a pin can slide in order to enable adisplacement of the respective positioning stop in the direction of thecentrally disposed force transmission element or away from the forcetransmission element. If one positioning stop moves in the direction ofthe center or another defined target point, the other positioning stopalso moves as a result of the force coupling in the direction of thecenter. Conversely, one positioning stop moves away from this centerwhen the other positioning stop is remote from this center.

The first linear guide elements can be oriented such that thepositioning stops are mounted displaceably parallel to one another. Thiscan be achieved, for example, by the linear guide grooves of the firstlinear guide elements being oriented substantially parallel to oneanother so that when they move, the positioning stops are displacedparallel to one another.

The first linear guide elements can in particular be oriented such thatthe positioning stops are mounted parallel displaceably offset withrespect to a diagonal of the main body. In other words, according tothis exemplary embodiment, the positioning stops in the first linearguide elements move parallel to one another but with a predefinedlateral offset. The positioning stops then do not move exactly in thedirection of a midpoint of the main body but miss the midpoint by apredefined lateral offset in the tangential direction during a continuedmovement. By this means a lever force can be efficiently transmittedbetween the force transmitting element and the positioning stops, whichcan lead to a rotation of the force transmitting element and thereforeto an efficient force transmission.

The second corner region of the main body (in which the actuatingelement can be disposed) can be different from the first corner regionsof the main body (in which the positioning stops are disposed).According to this exemplary embodiment there is therefore no cornerregion in which both the actuating element and also a positioning stopis disposed. This makes it possible to avoid undesirable interaction ofthese elements and leads to an advantageous transmission of force as aresult of the X configuration described above. At the center of this Xthe force transmitting element can clearly be mounted movably to enablea lever-like force transmission with predefinable lever arm lengths.

The actuating device can have a slider for manual actuation of theactuating device by a user. Such a slider can also be guided in a secondlinear guide device, i.e. for example, achieved by means of adisplaceable pin, which can be displaced in an elongated groove in apredefinable direction. A user is therefore protected from incorrectoperation of the apparatus since such an actuating device only enables aforward or backward movement for transferring the system between the twooperating states. A provision of the actuating device in a corner of themain body leads to a favorable lever arm which enables a low-forcetransfer of the system between the two operating states.

The slider can have a gripping piece, which can be formed in order tointuitively show a user that this is a gripping piece. For example, sucha gripping piece can have an arrow-shaped end section on which the usercan grip the actuating device. Both a pushing and a pulling is possiblewith such an arrow-shaped end section. Such a slider can, for example,be adjoined by two parallel struts which can enable a transmission offorce between the gripping piece and a pin sliding in the second linearguide direction.

The actuating device can comprise a coupling piece for coupling to anelectrical actuator device. According to this exemplary embodiment, anactuation of the actuating device can be made automatically by anelectronic control system without requiring any intervention of a user.An electrical actuator can be provided for this purpose, which, forexample, can function according to the servo motor principle.

In such an exemplary embodiment, the apparatus can comprise theelectrical actuator device itself. For example, the electrical actuatordevice can be integrated at least partially or completely in the mainbody. This electrical actuator device can engage in the coupling piecefor transmission of an electrical actuating force to the forcetransmitting element. In other words, the electrical actuator device cancooperate mechanically with the coupling piece in order to enable thetransmission of a force of electrical original to the actuating element.Such a force then leads directly to a movement of the positioning stopsaccording to a direction and an amplitude of this force.

For example, the electrical actuator device can comprise a drive shaftand a lever arm disposed thereon. The drive shaft can be equipped to berotatable and can rotate about its own axis. A transversely projectinglever arm can be provided mounted on the drive shaft, in the end sectionwhereof a coupling can be accomplished to a force transmitting pin orsimilar which can be movably disposed in a linear guide groove of thesecond linear guide device of the actuating element. In this way, theelectrical actuating force can be efficiently transmitted. Naturally, aplurality of alternatives are possible for this embodiment.

The apparatus can further comprise an electrically controllablepipetting device, which can be equipped for pipetting a fluid into wellsof the sample carrier plate. For example, a sample carrier plate can beused as a microtiter plate having 1536 wells, for example. This showsthat both the number of wells or saucers and also the requirements forthe positioning accuracy in such microtiter plates and similar samplecarrier plates is very high. A corresponding pipetting robot can controla plurality of pipettes, each of which can pipette in or pipette out apredefined amount of a predefined substance or a substance mixture intoan appurtenant well. Even with small positioning inaccuracies, thisprecise supply or removal of fluids in to the respective well can benegatively influenced. The positioning device according to the inventioncan thereby be used particularly advantageously with such an automaticpipetting device. In the case of an electronically controlled actuatingdevice, the electronically controllable pipetting device can becontrolled by the same electronic control unit (for example, a CPU,central processing unit) as the electrical actuator device. However, itis also possible that two separate control units can be used.

Alternatively or additionally to a pipetting device, the apparatus cancomprise a shaking device which can be equipped for shaking the samplecarrier plate mounted on the main body. While carrying out a biochemicalexperiment, it can be necessary or desirable that one or more componentsor substances poured into a respective well of the sample carrier plateare mixed with one another or are kept in mixing motion (for example, inorder to avoid a phase separation). Such mixing can be achieved by meansof a shaking movement. By means of the provision of the positioningstops according to the invention, a centering of the sample carrierplate relative to the apparatus can be maintained during or after ashaking movement.

For example, such a shaking apparatus can be implemented as is describedin FIG. 24, FIG. 25 and the following figures of WO 2008/135565. Theseexemplary embodiments are included in the disclosure of this patentapplication by means of explicit reference, which allows theconfiguration of a shaking device.

In particular, according to the invention, the shaking device can beequipped for acting upon the sample carrier plate with an orbitalmovement (for the purpose of shaking). It is possible, for example, thatone or more compensating weights is mounted on a, for example, eccentricdrive shaft of such a shaking apparatus so that an uncompensated mass ofthe apparatus can be at least partially compensated during the shakingmovement. In particular, two mutually opposite compensating weights canbe disposed along the shaft. It is also possible to avoid holdingtogether various components of the apparatus by means of magneticelements during the shaking.

The apparatus can further comprise a mechanical (or also electrical ormagnetic) prestressing device disposed in or adjacent to a third cornerregion of the main body, which can be equipped for transmitting aprestress (for example, a tensile prestress) to the force transmittingelement. Such a prestressing device can make up the X-type forcetransmitting configuration of an apparatus according to one exemplaryembodiment. Such a prestressing device for producing a tensile prestresscan represent the apparatus in a basic setting in which a clamping forceis exerted on the positioning stops as a result of the tensile stress.

The prestressing device can, for example, be a spring, in particular ahelical spring, which can be fastened in the third corner region and cantransmit a modified force to the positioning corners via the forcetransmitting element in order to initiate or terminate a clampingaction. Upon actuating the clamping device, however, the system can betransferred from this clamping state into a clamping-free state fromwhich the prestressing device can, however, exert a repelling force. Areturn of the system into the clamping state is thus possible withlittle expenditure of force.

If the prestressing device is configured as a spring, its one end can befastened to a main body, in particular in the third corner region of themain body (for example, rigidly). The other end can be coupled to theforce transmitting element. Such a spring can generate a repelling forcein an elongated state whereas it can exert a forward force in acompression state.

The second corner region (in which the actuating device can be disposed)can lie diagonally opposite the third corner region (in which theprestressing device can be disposed). Consequently, all four corners ofa substantially rectangular device can be provided with a correspondingfunctional component. These components can exert forces on one another,by making these forces act on the rotatably mounted force transmittingdevice which can then convert the force according to direction and/ormagnitude.

In the apparatus the force-transmitting element can comprise a rotatablymounted coupling disk, which can be coupled mechanically to theactuating device and the positioning stops. A coupling disk can beunderstood in particular as a flat disk-like arrangement, for examplehaving a circular base and top surface, which can be configured veryflat (for example, as a force transmitting plate). A rotatably mountedcoupling disk is therefore preferred since this enables a flat designand therefore a space-saving constructive form. For example, at thisrotatably mounted circular coupling disk, a circle diameter can be atleast three times, in particular at least five times, more particularlyat least ten times as great as a cylinder height. The actuating device,the positioning stops, and optionally the prestressing element can becoupled to an upper surface of such a coupling disk, which can bemounted rotatably about a midpoint in a central section. This can havethe result that a force originating from one of these elements can betransmitted to the other elements in a predefined manner. A lever armfor each element can be set to a desired higher or lower value byadjusting a radial spacing of the attachment of one of the elements to acircular surface.

A disk can be understood as the model of a flat surface supportingstructure that only stresses through forces in its plane and/or bendingmoments about axes perpendicular to its axis. Such a disk can, forexample, be implemented as a plate having circular top surfaces under acylindrical skin surface. In other words, a cylinder can be understoodas a disk whose thickness is many times smaller than its radius.

The apparatus can comprise first coupling rods, by which means arespective positioning stop can be coupled to the rotatably mountedcoupling disk. The first coupling rods can be coupled in an articulatedmanner to the rotatably mounted coupling disk and are connected to therespective positioning stop in an articulated manner by means of arespective first linear guide. Such coupling rods can be designed asrigid elongated struts which can have articulated bearings at two endsections. At these bearings such a first coupling rod can be disposedrotatably at a positioning stop (or at a first linear guide element of apositioning stop) in an articulated rotatable manner. An opposite secondend section of such a coupling rod can be mounted in an articulatedmanner on the rotatably mounted coupling rod. For example, such firstcoupling rods can be disposed near the center to an axis of rotation ofthe rotatably mounted coupling disk so that a relatively low lever armacts. This can be advantageous for the transmission of force in theapparatus according to the invention.

The first coupling rods can comprise a rectilinear section and can havean adjoining bent section. The bent section can, for example, bequadrant-shaped or semicircular-shaped. An efficient deflection of forceand low-wear mounting is possible by means of such a bent section. Ineach case, the first linear guide can adjoin the rectilinear sectionwhereas the bent section can be guided around the rotatably mountedcoupling disk, for example it can wind around a center of the rotatablymounted coupling disk along a circumferential angle of, for example, 90°or 180°.

A second coupling rod can further be provided, by which means theactuating device is coupled to the rotatably mounted coupling disk. Thesecond coupling rod can be connected in an articulated manner to therotatably mounted coupling disk and can be connected in an articulatedmanner to the actuating device by means of a second linear guide. Thissecond elongated coupling rod can therefore be interpreted as arotatably mounted strut on both end sections, which can enable atransmission of force between the rotatably mounted coupling disk on theone hand and the actuating device on the other hand.

According to one exemplary embodiment, the second coupling rod can bedisposed radially further outward on the rotatably mounted couplingdisk, in particular it can be disposed further outward than thecorresponding end sections of the first coupling rods in order to allowa large rotary lever arm.

The second coupling rods can be rectilinear, i.e. can extend linearlyalong a predefined direction. This can be advantageous for a rigid forcetransmission characteristic of this second coupling rod.

One of the first coupling rods and the second coupling rods can beconnected to a rotatably mounted coupling disk by means of a commonconnecting element (for example, a rotatable bearing). According to thisexemplary embodiment, a radial distance at which the first coupling rodsand the second coupling rods are coupled to the rotatably mountedcoupling disk can be identical. As a result, the number of connectingelements (i.e. for example, articulated bearings) can be kept small.

The apparatus can further comprise a third coupling rod, by which meansthe prestressing device can be coupled to the rotatably mounted couplingdisk. The third coupling rod can be connected in an articulated mannerto the rotatably mounted coupling disk. By means of such a thirdcoupling rod, a transmission of force between the prestressing device,in particular a helical spring, and the rotatably mounted coupling diskis made possible. Consequently, the prestressing of the spring can betransmitted to the rotatably mounted coupling disk. For the thirdcoupling rod it can also be advantageous for this to act on the couplingdisk radially further outward than the first coupling rods. For example,the radial distance at which the second and the third coupling rod acton the rotatably mounted coupling disk can be identical and correspondto substantially the same as the radius of the rotatably mountedcoupling disk.

The third coupling rod can also be provided to be rectilinear. Onelength of the third coupling rod can, for example, be smaller than onelength of the second coupling rod.

One of the first coupling rods and the third coupling rods can beconnected to one another by means of a common connecting element on therotatably mounted coupling disk. This again makes a simple structurepossible since a small number of common connecting elements issufficient.

In a configuration in which separate connecting elements are providedfor each of the first, second, and third coupling rods for mounting onthe coupling disk, these can be disposed in a coplanar manner. In otherwords, all the coupling rods can be disposed within a common plane whichenables a flat design. Such a configuration can also reduce or minimizeforces perpendicular to such a mounting plane, which can reduce the wearof the rotatably mounted elements and the coupling rods.

For example, the first coupling rods, the second coupling rods, and thethird coupling rod can be mounted on a planar (for example circular) topsurface of the coupling disk. In such a configuration, the lateralsurface of the disk can be free from a linkage of the coupling rods.Such a configuration can be easy to mount and due to selectiveadjustability of a respective mounting radius of the coupling rod inrelation to the rotatably mounted coupling disk, enables an adaptabilityof the lever arm to an associated task of the respective components. Afurther degree of freedom for the adjustability of the forcetransmission characteristic of the apparatus is thereby given.

According to one exemplary embodiment each of the first, second, andthird coupling rods can be connected to an appurtenant connectingelement on the rotatably mounted coupling disk. The connecting elementsto the first coupling rods can be mounted radially further inward on thecoupling disk than the connecting elements of the second and/or thirdcoupling rods. This enables a planar arrangement of the coupling rodsand therefore a space-saving design. At the same time, this enables adifferent degree of coupling forces.

The prestressing device and the actuating devices can also be mounted ina coplanar manner to one another, i.e. in the same plane. Thiscontributes further to the flat design of the apparatus.

A secure and positionally stable mounting of microtiter plates during apipetting process or a shaking process can thereby be rendered possible.A precise positioning and centering of the microtiter plate in relationto the carrier can be made, for example, by the centering in relation tothe midpoint of the microtiter plate.

According to one exemplary embodiment of the invention, the actuatingdevice and the force transmitting device can be coupled in such a mannerthat in the operating state engaging the sample carrier plate, the forcetransmitting element transmits a shaking force produced by the shakingdevice to the actuating device in such a manner that despite the actionof the transmitted shaking force, the actuating device remains in a restposition with respect to a carrier element (i.e. in particular a carrierplate on which the sample carrier plate is disposed directly orindirectly) of the main body. In other words, according to such anexemplary embodiment, it can be made possible that the actuating devicecan be actuated for clamping or unclamping the sample carrier plate inrelation to positioning stops so that in this direction of action, acorresponding force can be transmitted from the actuating device to thepositioning stops. Simultaneously however, after the clamping of thepositioning stops, such a coupling position of the actuating devicerelative to the force transmitting element can be brought about that anintroduction of force leading to a movement of the actuating device inthe inverse direction of action, i.e. acting on the actuating device, ismechanically blocked. This can be accomplished by deflecting a shakingforce having such a direction onto the actuating device so that this isoriented orthogonally to a, for example, linear direction ofdisplacement of the actuating device. A “direction of displacement” canbe understood in this connection as an axis along which the actuatingdevice can be displaced by a user or a robot whereas a displacementalong other axes, in particular along an axis perpendicular to thedirection of displacement is prevented.

In particular, the actuating device and the force transmitting elementcan be coupled by means of the second coupling rod in such a manner thatin the operating state engaging the sample carrier plate, the secondcoupling rod transmits the shaking force perpendicular to the directionof displacement of the actuating device. The second coupling rod can bebrought into different orientations to the direction of displacement ofthe actuating device. In an angular or oblique position between thesecond coupling rod and the direction of displacement, at least oneforce component different from zero can act in the direction ofdisplacement so that a transmission of force is possible. In anorthogonal or at least substantially orthogonal (i.e. differing from aright angle by a few degrees) position between the second coupling rodand the direction of displacement, no force component (or at least noneovercoming any adhesive friction) can act in the direction ofdisplacement so that a transmission of force is blocked. Such aconfiguration therefore enables on the one hand a clamping of the samplecarrier plate by means of low-force actuation of the actuating deviceand on the other hand, when the sample carrier plate is clamped,inhibits a back-transmission of a force, in particular triggered by ashaking movement of a shaking plate, to the actuating device.

An exemplary embodiment of the invention connects an orbital mixing bymeans of magnetic guidance to a centric clamping of a microplate. Anadvantageous aspect is that the centric clamping can be combined inconjunction with the shaking/mixing. During shaking the microplateshould be clamped automatically in a centric manner in order to reliablyhold the microtiter plate in particular for high mixing speeds orshaking speeds since the microtiter plate could otherwise be undesirablydetached from the apparatus. The shaker itself always stops in its zeroposition, where the centric clamping aligns the microtiter plate soprecisely that highly precise pipetting into the wells is made possible.Particularly in the case of 384- or 1536-well microtiter plates and welldiameters becoming ever smaller, this is an important requirement forautomatic pipetting. The automatic opening on the one hand allows theclamping and on the other hand the release of the plate for an exchangeof the microtiter plate taking place automatically by robot gripper.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the present invention are described in detailhereinafter with reference to the following figures.

FIG. 1 shows a plan view of a positioning device according to anexemplary embodiment of the invention in an operating state in which asample carrier plate not shown is released.

FIG. 2 shows the positioning device from FIG. 1 in another operatingstate in which the sample carrier plate (not shown) is engaged by thepositioning corners.

FIG. 3 shows a positioning and carrier apparatus according to anotherexemplary embodiment on which a microtiter plate is mounted.

FIG. 4 shows the positioning apparatus according to FIG. 3 without coverplate and microtiter plate.

FIG. 5 shows an arrangement similar to FIG. 4 in plan view in which arotatably mounted coupling disk, a prestressing spring and a number ofcoupling rods are omitted for better visibility.

FIG. 6 shows the apparatus from FIG. 3 to FIG. 5 in a closed or amicrotiter plate-engaging state.

FIG. 7 shows the positioning apparatus according to FIG. 3 to FIG. 6 inan open or microtiter plate-releasing state.

FIG. 8 shows a positioning apparatus according to another exemplaryembodiment of the invention without mounted microtiter plate and withadapter plate in place.

FIG. 9 shows the positioning apparatus according to FIG. 8 in plan viewafter removing the adapter plate.

FIG. 10 shows the positioning apparatus according to FIG. 8 or FIG. 9 inthe alternative operating state to FIG. 9.

FIG. 11 shows the positioning apparatus according to FIG. 8 to FIG. 10with microtiter plate in place.

FIG. 12 shows a positioning apparatus according to another exemplaryembodiment of the invention with a microtiter plate.

FIG. 13 shows a cross-section through an interior of a carrier body ofthe positioning apparatus according to FIG. 12 and therefore illustratesa section through a mechanism with an inserted flat-bottom microtiterplate.

FIG. 14 shows the positioning apparatus according to FIG. 12 and FIG. 13and in particular a mechanism with a round-bottom microtiter plate andadapted adapter plate.

FIG. 15 shows a mechanism with round-bottom microtiter plate and adaptedadapter plate from below in accordance with the positioning apparatusaccording to FIG. 12 to FIG. 14.

FIG. 16 shows a section of the positioning apparatus according to FIG.12 to FIG. 15 through a mechanism with inserted round-bottom microtiterplate.

FIG. 17 shows a section along the line of intersection A-A according toFIG. 9.

FIG. 18 shows a partial view of the positioning apparatus according toFIG. 12 to FIG. 17 in which the position of a servo motor mechanism isclosed.

FIG. 19 shows the position of the servo motor open, and

FIG. 20 shows a sectional view through a linear guide of the mechanism.

FIG. 21 and FIG. 22 show in plan view schematic diagrams of apositioning device according to one exemplary embodiment of theinvention where in an operating state shown in FIG. 21, a sample carrierplate can be clamped between positioning stops by actuating an actuatingdevice and where in an operating state shown in FIG. 22, the samplecarrier plate is shaken, clamped between positioning stops, without theshaking force undesirably setting the actuating device in motion.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The diagrams in the figures are schematic and not to scale.

The same or similar components in different figures are provided withthe same reference numbers.

With reference to FIG. 1 and FIG. 2, a sample handling device 100according to an exemplary embodiment of the invention will be describedhereinafter.

The sample handling device 100 contains a rectangular main body 102shown in plan view, having four right-angled corner regions. A carrier104 is provided as an elevation in a cavity in the main body 102, inwhich a plurality of different components of the sample handling device100 are accommodated.

The main body 102 can contain the carrier 104. Main body 102 and carrier104 can be formed as a common integral component or they can be formedas separable components. The main body 102 can have a fixed base housingand the carrier 104 can be mounted movably.

After the carrier 104 is mounted in the cavity of the main body 102, arecess can remain above the carrier 104 and delimited laterally by thecarrier 104 of the main body 102, which can be covered by inserting anadapter plate (see, for example, FIG. 8) not shown in FIG. 1 and FIG. 2.

Two first and cooperating stop elements, designed as conical pins 108,are disposed in an upper left corner region of the carrier 104 accordingto FIG. 1. Two cooperating second conical positioning pins 106 whichtaper into the plane of the paper in FIG. 1 are mounted in an oppositecorner region of the carrier 104. As is explained in detail hereinafter,the positioning stops 106, 108 are used to clamp a sample carrier platenot shown in FIG. 1, such as a microtiter plate for example.

The first positioning stops 108 are functionally operatively coupled toa first linear guide device 110. In other words, under the action of acorresponding force on the first positioning stops 108, these aredisplaced in the direction of a center 111 of the sample handling device100, whereby the first positioning stops 108 slide in a groove of thefirst linear guide device 110.

Accordingly, the second stop elements 106 can slide in an associatedlinear guide device 112 so that these can either be displaced jointlywith the first positioning stops 108 in the direction of the center 111or slide jointly with the first positioning stops 108 away from thecenter 111 toward the corresponding corners of the carrier 104.

An actuating device 114 is accommodated in another corner region of thecarrier 104, which in the exemplary embodiment according to FIG. 1 caneither be actuated by hand or manually by a human user by displacing atriangular end section of the actuating device 114 in the diagonaldirection in relation to the main body 102. Alternatively, the drive canbe accomplished using an electrical actuator device. The latter isdescribed in detail below.

By means of actuating the actuating device 114, the positioning stops106, 108 can each be transferred jointly between an operating stateengaging the sample carrier plate and an operating state releasing thesample carrier plate, i.e. not engaging this plate. FIG. 1 shows thereleased operating state in which the positioning stops 106, 108 arepushed FIG. 2 on the other hand show the engaging operating state inwhich the positioning stops 106, 108 are disposed closer to the center111 of the carrier 104 than according to FIG. 1.

As can be identified from FIG. 1, the released operating statecorresponds to a position of the actuating device 114 closer in relationto the center 111 than the engaging operating state according to FIG. 2,in which the arrow-like end section of the actuating device 114 projectsslightly beyond the corresponding corner region of the carrier 104.

A circular disk 118 mounted rotatably, i.e. capable of rotation (seereference number 116) in the center 111 is provided as aforce-transmitting element which transfers an actuating force from theactuating device 114 to the positioning stops 106, 108 in such a mannerthat a displacement of the positioning stops 106, 108 inward (i.e. inthe direction of the center 111) or outward (i.e. away from the center111) can necessarily be accomplished by means of displacement of theposition of the actuating element 114 between the positions shown inFIG. 1 and FIG. 2.

With the sample handling device 100 it is thus possible for a microtiterplate having a substantially rectangular cross-section to be placed onthe central section of the carrier 104 and directly adjoin thepositioning stops 106, 108 in two opposite corner regions when thesystem is in the closed state according to FIG. 2. In the open stateaccording to FIG. 1 a distance remains between the positioning stops106, 108 and the microtiter plate.

The force transmitting mechanism described is thus used to center themicrotiter plate in relation to the midpoint 111 of the carrier 104 or afixed point of the main body 102.

As in each of the exemplary embodiments disclosed here, in the samplehandling device 100 shown in FIG. 1, an optional shaking device can beintegrated in the main body 102 and carrier 104 (not shown) which can beconfigured in such a manner that the microtiter plate executes anorbital movement between the positioning stops 106, 108 upon receptionand consequently fluids contained in wells of a microtiter plate (forexample, a liquid and/or a gas, with solid components not beingexcluded) can be reliably mixed. The clamping action of the positioningstops 106, 108 in the closed position according to FIG. 2 can hold themicrotiter plate securely and centered, when averaged over time, withrespect to the center 111 even during such an orbital movement.

The force transmission mechanism described cooperates with a helicalspring 120 serving as a prestressing device, which is disposed in theremaining corner region of the main body 102 (see FIG. 1 and FIG. 2).Consequently, either an appurtenant positioning stop 106 or 108 or theactuating device 114 or the spring 120 is provided in each corner regionof the rectangular carrier 104. This results in the X-shaped forcetransmission geometry shown clearly in FIG. 1, which cooperates with therotatably mounted force transmitting disk 118 as mediator.

The helical spring 120 can be prestressed in such a manner that thistransmits a tensile prestress to the rotatably mounted coupling disk118. One end of the spring 120 is fastened to the carrier 104, with theother end being coupled via a coupling rod 152 and via a connectingelement 122 to the coupling disk 118.

The sample handling device 100 comprises bent coupling rods 124 and 126.The bent coupling rod 124 couples the positioning stops 108 to thecoupling disk 118. In so doing, a connecting element 128 effects anarticulated connection between the linear guide device 1110 and arectilinear section 130 of the bent coupling rod 124. A substantiallysemicircularly bent section 132 of the coupling rod 124 is connected inan articulated manner via a connecting element 134 to the coupling disk118.

A distance r₁ between the center 111 and a center of the connectingelement 134 is designated as r₁ in the exemplary embodiment according toFIG. 1 and is the same as the distance r₂ separating the connectingelement 136 from the center 111. The connecting element 136 connects abent end section 138 of the bent coupling rod 126 in an articulatedmanner to the circular disk 118. The bent coupling rod 126 also containsa straight section 140 which is coupled in an articulated manner via aconnecting element 142 to the linear guide device 112, which isassociated with the positioning stops 106.

A rectilinearly extending coupling rod 144 connects the actuating device114, more accurately a linear guide device 146 of the actuating device114, to the rotatably mounted coupling disk 118. For this purpose thecoupling rod 114 contains a connecting element 148 for the articulatedconnection of the coupling rod 144 to the linear guide device 146. Aconnecting element 150 connects the coupling rod 144 in an articulatedmanner to the coupling disk 118.

Finally the further coupling rod 152 is provided which couples thehelical spring 120 to the rotatably mounted coupling disk 118 in anarticulated manner.

A radial distance between the center 111 and a center of the connectingelement 150 is designated by r₃ whereas a radial distance between thecenter 111 and the connecting element 122 is designated by r₄. In theembodiment described it holds that r₁=r₂, r₃=r₄ and r₃>r₁.

A favorable lever system for the transmission of force is thus provided.

In the exemplary embodiment according to FIG. 1, the coupling rods 124,126, 152 and 144 are designed as thin but rigid metal strips which areall disposed in the same plane, i.e. on an upper circular top surface ofthe thin disk-shaped metal body which forms a coupling surface of thecoupling disk 118. A very space-saving flat design is thereby madepossible.

FIG. 3 shows a three-dimensional view of a sample handling device 300according to another exemplary embodiment of the invention.

In this exemplary embodiment, a microtiter plate 302 is placed on thecarrier 104 and held laterally fixed. According to the exemplaryembodiment of FIG. 3, this is achieved by means of stop elements 304 or306 in opposite corner regions of the carrier 104, which nestle againstside walls of the microtiter plate 302 with mutually perpendicularlydisposed stop lines 308, 310 along a cohesive line. The microtiter plate302 contains a plurality of wells or sample receiving saucers 312arranged in a matrix shape.

FIG. 4 shows a view of the sample receiving apparatus 300 after themicrotiter plate 302 and an adapter plate disposed in a central regionof the main body have been removed. This adapter plate can be mountedpositively in a recess 400 and screwed, for example, and can be heldwith a bottom surface on a ring-like bottom section in the recess 400and held simultaneously with side surfaces on a circumferential sidewall of the recess 400.

Unlike the exemplary embodiment according to FIG. 1 and FIG. 2, in theexemplary embodiment according to FIG. 4 the various coupling rods arepartially coupled to common points on the coupling disk 118, as will bedescribed in detail with reference to FIG. 6 and FIG. 7. There it isshown in detail how the coupling rods 152, 126 are interconnected in anarticulated manner by means of the connecting element 402 and thecoupling rods 144 and 142 are interconnected in an articulated manner bymeans of a connecting element 404.

As a result of these common connecting elements 402, 404 forrespectively two of the coupling rods, the coupling rods are not alllaid exactly in a common plane but in two adjoining or neighboringplanes. In the arrangement 300 the coupling rods 124, 126 are locatedfurther down with respect to the adapter surface than the coupling rods152, 144.

FIG. 5 illustrates a view for the sample handling device 300 after aseries of components shown in FIG. 4 has been dismounted.

It can be deduced from FIG. 5 in particular that a line of sight 502 ofthe guide groove of the linear guide device 110 is disposed parallel toa line of sight 504 of the elongate hole of the linear guide device 112.Both lines of sight 502 and 504 are disposed substantially along adiagonal of the rectangular carrier 104 and parallel to one another.They are laterally offset by a distance d with respect to one another. Aparticularly efficient transmission of forces is possible due to thisgeometry.

FIG. 6 shows a closed state and FIG. 7 shows an unlocked state of thesample handling device 300 with respect to the microtiter plate.

A functioning mode of the exemplary embodiment from FIG. 3 to FIG. 7 isdescribed once again hereinafter.

FIG. 3 shows the microtiter plate 302 which is inserted in thepositioning apparatus 300. FIG. 4 shows the mechanism which enables apositioning and fixing of the microtiter plate 302 with the carrier 104,comprising a disk 118 which is mounted rotatably with respect to thecarrier 104 via a bearing. The mechanism further comprises a spring 120fastened to the carrier and respectively two straight coupling rods 144,152 and two partially bent coupling rods 124, 126. At their ends thecoupling rods are connected on one side to the disk 118 in anarticulated manner. On their respectively other side the coupling rods124, 126, 144 are connected to the linearly guided sliders 110, 112, 146in an articulated manner. The coupling rod 152 is connected with thesecond side to the carrier 104 via a spring 120. With regard to the typeof connection of the bent coupling rods 124, 126 and the disk 118, seealso FIG. 6 and FIG. 7. The positioning corners 304, 306 are eachconnected to the two sliders 110, 112.

FIG. 5 shows the structure of an exemplary embodiment of the carrier104. Here it can be identified that the sliders 110, 112 each carryingthe positioning corners 304, 306 are each guided in two linear guideswhich are aligned parallel to one another. A shape which projects intothe linear guides is located on the sliders 110, 112 on the undersidethereof.

If the slider 114 is displaced manually or automatically in the linearguide 146, this linear displacement is then transmitted via coupling rod144 to the disk 118 which is moved against the force transmitted by thespring 120 via coupling rod 152 until the slider 146 is stopped at thestop in the associated guide groove. As a result, the sliders with thepositioning pieces 304, 306 affixed thereon are displaced along theguides 110, 112 via the coupling rods 124, 126. In this position themicrotiter plate 302 can be inserted into the carrier 104. When thestrain on the slider 146 is released, the disk 118 is twisted by thespring force acting via coupling rod 152 and spring 120 into the initialposition, whereby sliders 110, 112 and positioning pieces 304, 306 aredisplaced as far as the edge of the base of the microtiter plate 302.The open and closed state of the mechanism is shown in FIG. 6 or FIG. 7.

During an orbital shaking movement, a centrifugal force having acirculating direction of action acts on the microtiter plate 302 and theliquids contained therein. Since however, the positioning pieces 304,306 are guided linearly on the sliders 110, 112, only one possibledegree of freedom of the movement is obtained as a result of thecentrifugal force, which is represented by the indicated arrows in FIG.6.

A fundamental improvement of the mechanism compared with conventionalsystems is that the articulation point of the coupling rods 124, 126 ispositioned on the rotatably mounted disk 118 in the closed state suchthat a very low effective lever arm, ideally lever arm=0, is obtainedwith respect to the pivot point of the disk 118. This has the resultthat due to the centrifugal force, a very small torque is exerted on thedisk 118 whereas the effective lever arm of the prestressed spring 120on the disk 118 is large and in this exemplary embodiment corresponds tothe pitch circle radius of its linkage.

As a result, the advantage is obtained in particular that a very rigidconnection of positioning piece 304, 306 and microtiter plate 302 can beachieved with a very small spring force. Despite this rigid connection,in the opened state the mechanism can be equipped with the microtiterplate 302 in forceless manner. Another advantage of this mechanism liesin the centering of the microtiter plate 302 with regard to the carrier104. The manufacturing tolerances of length and width of the microtiterplates 302 therefore do not influence the position of the wells inrelation to the center of the carrier 104.

FIG. 8 shows a sample handling device 800 according to another exemplaryembodiment of the invention in which an adapter plate 802 is inserted inthe recess 400.

As shown in FIG. 8, the adapter plate 800 ends flat with an adjoiningsurface region of the carrier 104.

FIG. 9 shows the sample handling device 800 after removing the adapterplate 802 in which, for example, a temperature control unit can beintroduced for controlling the temperature of a microtiter plate (notshown).

FIG. 9 shows the non-engaging operating state and FIG. 10 shows theengaging operating state of the sample handling device 800.

In FIG. 11 the microtiter plate 302 is received on the adapter plate802.

A functioning mode of the exemplary embodiment from FIG. 8 to FIG. 11 isdescribed once again hereinafter.

FIG. 11 shows the microtiter plate 302 which is inserted in thepositioning apparatus 800. FIG. 8 to FIG. 11 further shows the mechanismwhich enables a positioning and fixing of the microtiter plate 302. Thisconsists of a carrier plate, a disk 118 which is mounted rotatably withrespect to the carrier 104 via the bearing 112. The mechanism furthercomprises a spring 120 fastened to the carrier and respectively twostraight coupling rods 144, 152 and two partially bent coupling rods124, 126. At their ends the coupling rods are connected on one side tothe disk 118 in an articulated manner. On their respectively other sidethe coupling rods 124, 126, 144 are connected to the linearly guidedsliders 110, 112, 146 in an articulated manner. The linear guidance isachieved via T-groove blocks (relevant guide slots 1002 and 1004 areshown in FIG. 10). The coupling rod 152 is connected with the secondside to the carrier 104 via a spring 120. Two conical pins 106, 108 areattached to each of the two sliders 110, 112, by which the microtiterplate 302 is centered and fixed non-positively. If the slider 114 islinearly displaced, manually or automatically, this linear displacementis then transmitted via coupling rod 144 to the disk 118 which is movedagainst the force transmitted by the spring 120 via coupling rod 152until the slider 146 is stopped at the stop in the associated guidegroove 1000. As a result, the sliders 110, 112 with the positioningpieces 106, 108 affixed thereon are displaced along the guides 1002,1004. In this position the microtiter plate 302 can be inserted into themechanism. When the strain on the slider 114 is released, the disk 118is twisted by the spring force acting via coupling rod 152 and spring120 into the initial position, whereby sliders 110, 112 and conical pins106, 108 attached thereto are displaced as far as the edge of the baseof the microtiter plate 302. The open state is shown in FIG. 9 and theclosed state of the mechanism is shown in FIG. 10.

During an orbital shaking movement, a centrifugal force having acirculating direction of action acts on the microtiter plate 302 and theliquids contained therein. Since however, the conical pins 106, 108 areguided linearly on the sliders 110, 112, only one possible degree offreedom of the movement is obtained as a result of the centrifugalforce. An improvement of the mechanism compared with conventionalsystems is that the articulation point of the coupling rods 124, 126 ispositioned on the rotatably mounted disk 118 in the closed state suchthat a very low effective lever arm, ideally lever arm=0, is obtainedwith respect to the pivot point of the disk 118. This has the resultthat due to the centrifugal force, a very small torque is exerted on thedisk 118 whereas the effective lever arm of the prestressed spring 120on the disk 118 is large. This has the advantage that a very rigidconnection of positioning pins 106, 108 and microtiter plate 302 can beachieved with a very small spring force. Despite this rigid connection,in the opened state the mechanism can be equipped with the microtiterplate in a forceless manner. Another advantage of this mechanism lies inthe centering of the microtiter plate 302 with regard to the carrier.The manufacturing tolerances of length and width of the microtiterplates 302 therefore do not influence the position of the wells inrelation to the center of the carrier 104.

One improvement is that now all the elements lie in one plane and as aresult the overall height of the mechanism is substantially reduced. Inaddition, due to the conical pins 106, 108, it is relatively easilypossible to adapt the mechanism to other objects and geometries.

FIG. 12 shows a sample handling device 1200 according to yet anotherexemplary embodiment of the invention. FIG. 13 shows a section throughthe basic mechanism with inserted flat-bottom microtiter plate 302.

FIG. 14 shows a sample handling device 1400 according to yet anotherexemplary embodiment of the invention in which a microtiter plate 1402with a structured underside (see FIG. 15) is placed on a correspondinglyshaped adapter plate 1404.

Accordingly, an upper side of the adapter plate 1404 according to FIG.14 is provided with a topography such that projections 1500 on theunderside of the microtiter plate 1402 can engage seamlessly in wells1406 of the adapter plate 1404.

FIG. 16 shows a view in which the round-bottom microtiter plate 1402 isplaced seamlessly on the adapter surface 1404.

Again with reference to FIG. 9, a line of intersection A-A is shownthere along which the section 1700 illustrated in FIG. 17 is shown. Theconfiguration of the actuating element 114 can also be seen in detailfrom FIG. 17.

FIG. 18 shows a position of a servomotor mechanism in a closed statewhile FIG. 19 shows the corresponding situation for an open state. Thisservo is characterized by reference number 1800.

FIG. 19 shows a lever arm 1900 which presses against a pin or screw head1902. The linear guidance of the slider 114 is accomplished via a groovein these sliders using a groove block 2000 which is shown in FIG. 20.

An functioning mode of the exemplary embodiments from FIG. 12 to FIG. 20is described once again hereinafter.

FIG. 12 shows a microtiter plate 392 having a flat bottom. FIG. 13 showsa section through the mechanism with inserted flat-bottom microtiterplate 1402. The adapter plate 802 which enables a temperature control ofthe microtiter plate 1402 fixes the microtiter plate 1402 onlyvertically. The microtiter plate 1402 remains movable horizontallywithout the action of the positioning pieces 106, 108.

FIG. 14 shows the mechanism with a microtiter plate having a roundbottom and an adapter plate 1404 adapted to this shape. FIG. 15 showsthe shape of the bottom of the microtiter plate 1402. FIG. 16 shows asection through the mechanism with inserted microtiter plate 1402. Itcan be seen here that when using a microtiter plate having a profiledbottom without the action of positioning pieces 106, 108, a certainhorizontal securing of the microtiter plate 1402 is accomplished.

The mechanism is either actuated manually by actuating the slider 114 orby an electrical actuator. These facts of the matter are shown in FIG.18 to FIG. 20. The automated actuation can be accomplished by a servo1800 having a lever arm 1900 attached to its shaft, which pressesagainst a pin or here screw head 1902. As a result, this is displacedinside the groove and the mechanism thereby opened. In the closed statelever arm 1900 and screw head 1902 do not contact. The screw head isconnected to the slider 114 via a thread and a joint.

The linear guidance of the three sliders is accomplished via a groove inthese sliders and a groove block 2000. In FIG. 20 the functioning modeis shown for the example of a slider. The linear guidance of the othersliders functions similarly.

The conical pins 106, 108 are fastened on the sliders by screwing. As aresult, these elements can be exchanged by the user in a particularlysimple manner. The mechanism can thus be adapted to different geometriesand different base heights of the microtiter plate rapidly anduncomplicatedly.

FIG. 21 and FIG. 22 show in plan view schematic diagrams of apositioning device 2100 according to one exemplary embodiment of theinvention. The arrangement can be configured similarly to that shown inFIG. 1 so that only the components relevant for explaining thefunctioning principle of a movement block for preventing any movement ofan actuating device 114 as a result of a shaking of a sample carrierplate are shown in FIG. 21 and in FIG. 22. If the positioning stops arelocated in opposite corner regions of the positioning device 2100, thecorresponding forces should be suitably deflected, for example, by usingsuitable coupling rod geometries with respect to the schematic diagramin FIG. 21 and FIG. 22.

In an operating state shown in FIG. 21, a sample carrier plate, notshown, is inserted between positioning stops, not shown, by actuatingthe actuating element 114. If the actuating element 114 is pushed upwardin the direction of an arrow 2102 according to FIG. 21, the coupling rod144 is thereby tilted, leading to a twisting of the force transmittingdisk 118. As a result, the coupling rods 124, 126 are also twisted, withthe result that sliders of the linear displacement devices 110, 112 aredisplaced along linear displacement directions 2104, 2106 andconsequently positioning stops are pressed outward.

In an operating state shown in FIG. 22 the sample carrier plate isalready clamped between the positioning stops and is shaken by means ofa shaking device (not shown) without the shaking force undesirablysetting the actuating device 114 in motion. This is accomplished using aforce transmission mechanism which is described hereinafter.

The actuating element 114 and the force transmitting disk 118functioning as force transmitting element are coupled by means of thecoupling rod 144 in such a manner that a shaking force of the shakingdevice is transmitted to the actuating element 114 in such a manner thatdespite the action of the transmitted shaking force, the actuatingelement 114 remains in the rest position according to FIG. 22, i.e. doesnot move up or down according to FIG. 22. The actuating element 114 andthe force transmitting disk 118 are coupled by means of the coupling rod144 in such a manner that in the operating state according to FIG. 22the coupling rod 144 couples in the shaking force, cf. reference number2202, perpendicular to a displacement direction 2108 of the actuatingelement 114.

In an orthogonal position between the coupling rod 144 and thedisplacement direction 2108 according to FIG. 22, no shaking forcecomponent can lead to a movement of the actuating element 114 so thatthis type of force transmission advantageously blocks the movement. Inthe other force transmission direction, i.e. from the actuating element114 to the linear guide devices 110, 112, on the other hand a forcetransmission leading to a movement can take place since the couplingrods 124, 126 are not perpendicular (but even approximately parallel) tothe linear displacement directions 2104, 2106.

In the closed state according to FIG. 22, an angle of almost 90° can beachieved between coupled-in shaking force 2202 and displacementdirection 2108. The system is then so well clamped that springs couldalso be omitted. The system can almost not be pushed open over thecorners and also reliably withstands very high shaking speeds.

In addition, it should be noted that “comprising” does not exclude anyother elements or steps and “an” or “a” does not exclude a plurality. Itshould also be noted that features or steps which have been describedwith reference to one of the above exemplary embodiments can also beused in combination with other features or steps of other exemplaryembodiments described above. Reference numbers in the claims are not tobe construed as a restriction.

What is claimed is:
 1. An apparatus for positioning a sample carrierplate, wherein the apparatus comprises: a main body for receiving thesample carrier plate; positioning stops, which are disposed indiagonally opposing first corner regions of the main body and areprestressed for clamping the sample carrier plate and mounteddisplaceably; an actuating device which is disposed at the main body andis adapted such that by actuating the actuating device, the positioningstops can be transferred between an operating state engaging the samplecarrier plate and an operating state releasing the sample carrier plate;a force transmitting element which is adapted to transmit an actuatingforce from the actuating device to the positioning stops, the forcetransmitting element comprises a rotatably mounted coupling disk,wherein the rotatably mounted coupling disk is coupled to the actuatingdevice and the positioning stops, a plurality of first coupling rods,each of which is coupled to the respective positioning stop and to therotatably mounted coupling disk, wherein the first coupling rods arepivotably connected in an articulated manner by a first rotatableconnecting element to the rotatably mounted coupling disk, a secondcoupling rod by which the actuating device is pivotably coupled to therotatably mounted coupling disk, wherein the second coupling rod ispivotably connected in an articulated manner by a second rotatableconnecting element to the rotatably mounted coupling disk and ispivotably connected in an articulated manner by a third rotatableconnecting element to the actuating device.
 2. The apparatus of claim 1,wherein the main body comprises an adapter plate for receiving thesample carrier plate, wherein the adapter plate is a flat adapter platefor positive receipt of a flat sample carrier plate, and wherein themain body has a recess in which the adapter plate can be inserted sothat it ends flush on an upper side.
 3. The apparatus of claim 2,wherein the adapter plate has a surface structure which is adapted forthe positive receipt of a sample carrier plate having a surfacestructure complementary to the surface structure of the adapter surface.4. The apparatus of claim 1, wherein the positioning stops are disposedexclusively at two opposite first corner regions of the main body,wherein the positioning stops in each first corner region are formed bymeans of two stop elements having two mutually perpendicular stop linesfor placement on a rectangular sample carrier plate, wherein thepositioning stops in each first corner region are formed by means of twostop elements having a round cross-section for placement on the samplecarrier plate.
 5. The apparatus of claim 1, wherein each of thepositioning stops is assigned a first linear guide element in which therespective positioning stop is mounted linearly displaceably, whereinthe first linear guide elements are oriented such that the positioningstops are mounted displaceably parallel to one another, wherein thefirst linear guide elements are adapted such that the positioning stopsare mounted displaceably and parallel offset with respect to a diagonalof the main body.
 6. The apparatus of claim 1, wherein the actuatingdevice comprises a slider for manual actuation by a user, wherein theslider has a gripping piece having an arrow-shaped end section.
 7. Theapparatus of claim 1, wherein the actuating device comprises a couplingpiece for coupling to an electrical actuator device, the apparatusfurther comprising the electrical actuator device, which engages in thecoupling piece for transmission of an electrical actuating force to theforce transmitting element, wherein the electrical actuator devicecomprises a drive shaft and a lever arm disposed thereon, which acts ona force transmitting pin for transmission of the electrical actuatingforce, which pin is disposed movably in a linear guide groove of theactuating element.
 8. The apparatus of claim 1, further comprising aprestressing device disposed adjacent to a third corner region of themain body, which is adapted for transmitting a prestress, in particulara tensile prestress, to the force transmitting element, whereinoptionally the prestressing device comprises a spring, one end of whichis fastened to the main body and the other end of which is coupled tothe force transmitting element, wherein further the second corner regionlies opposite the third corner region.
 9. The apparatus of claim 8,wherein the rotatably mounted coupling disk is coupled to theprestressing device, wherein the first coupling rods are coupled in anarticulated manner to the rotatably mounted coupling disk and areconnected to the respective positioning stop in an articulated manner bymeans of a respective first linear guide, wherein the first couplingrods comprise a rectilinear section, which adjoins the respective firstlinear guide and comprise a bent section, which is guided around therotatably mounted coupling disk.
 10. The apparatus of claim 1, whereinthe second coupling rod is connected in an articulated manner to therotatably mounted coupling disk and is connected in an articulatedmanner to the actuating device by means of a second linear guide,wherein the second coupling rod is rectilinear, wherein one of the firstcoupling rods and the second coupling rod are connected to the rotatablymounted coupling disk by means of a common connecting element.
 11. Theapparatus of claim 9, further comprising a third coupling rod, by whichthe prestressing device is coupled to the rotatably mounted couplingdisk, wherein the third coupling rod is connected in an articulatedmanner to the rotatably mounted coupling disk, wherein the thirdcoupling rod is rectilinear, wherein one of the first coupling rods andthe third coupling rod are connected by means of a common connectingelement to the rotatably mounted coupling disk, wherein the firstcoupling rods, the second coupling rod, and the third coupling rod aredisposed in a coplanar manner, wherein the first coupling rods, thesecond coupling rod, and the third coupling rod are mounted on acircular top surface of the coupling disk, wherein each of the firstcoupling rods are connected by means of an appurtenant connectingelement on the rotatably mounted coupling disk and the connectingelements of the first coupling rods are mounted radially further inwardon the coupling disk than the connecting elements of the other couplingrods.
 12. The apparatus of claim 8, wherein the prestressing device andthe actuating device are mounted in a coplanar manner.
 13. A method forpositioning a sample carrier plate, wherein the method comprises:receiving the sample carrier plate on a main body of a device; clampingthe sample carrier plate on prestressed and displaceably mountedpositioning stops, which are disposed in diagonally opposite firstcorner regions of the main body; actuating an actuating device disposedat the main body for transferring the positioning stops between anoperating state engaging the sample carrier plate and an operating statereleasing the sample carrier plate; and transmitting an actuating forcefrom the actuating device to the positioning stops by means of arotatably mounted coupling disk, wherein the rotatably mounted couplingdisk is coupled to the actuating device and the positioning stops, andwherein a plurality of first coupling rods are coupled to the respectivepositioning stop and to the rotatably mounted coupling disk, wherein thefirst coupling rods are pivotably connected in an articulated manner bya first rotatable connecting element to the rotatably mounted couplingdisk, wherein the actuating device is coupled to the rotatably mountedcoupling disk by a second coupling rod; wherein the second coupling rodis pivotably connected in an articulated manner by a second rotatableconnecting element to the rotatably mounted coupling disk and isconnected in an articulated manner by a third rotatable connectingelement to the actuating device.